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Protein

Heat shock 70 kDa protein 6

Gene

HSPA6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei73ATP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi14 – 17ATP4
Nucleotide bindingi204 – 206ATP3
Nucleotide bindingi270 – 277ATP8
Nucleotide bindingi341 – 344ATP4

GO - Molecular functioni

  • ATPase activity, coupled Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • enzyme binding Source: BHF-UCL
  • heat shock protein binding Source: UniProtKB
  • unfolded protein binding Source: UniProtKB

GO - Biological processi

  • cellular response to heat Source: UniProtKB
  • neutrophil degranulation Source: Reactome
  • protein refolding Source: UniProtKB
  • response to unfolded protein Source: ProtInc

Keywordsi

Biological processStress response
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-6798695 Neutrophil degranulation
SIGNORiP17066

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock 70 kDa protein 6
Alternative name(s):
Heat shock 70 kDa protein B'
Gene namesi
Name:HSPA6
Synonyms:HSP70B'
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000173110.7
HGNCiHGNC:5239 HSPA6
MIMi140555 gene
neXtProtiNX_P17066

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi563K → R: Complete loss of in vitro methylation by METTL21A. 1 Publication1

Organism-specific databases

DisGeNETi3310
OpenTargetsiENSG00000173110
PharmGKBiPA29505

Chemistry databases

ChEMBLiCHEMBL3232688

Polymorphism and mutation databases

BioMutaiHSPA6
DMDMi34978357

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000782641 – 643Heat shock 70 kDa protein 6Add BLAST643

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei563N6,N6,N6-trimethyllysine; by METTL21A; in vitro1 Publication1

Keywords - PTMi

Methylation

Proteomic databases

EPDiP17066
MaxQBiP17066
PaxDbiP17066
PeptideAtlasiP17066
PRIDEiP17066

2D gel databases

UCD-2DPAGEiP17066

PTM databases

iPTMnetiP17066
PhosphoSitePlusiP17066
SwissPalmiP17066

Expressioni

Inductioni

Only at higher temperatures, and no basal expression.

Gene expression databases

BgeeiENSG00000173110
CleanExiHS_HSPA6
GenevisibleiP17066 HS

Organism-specific databases

HPAiCAB017452
HPA028549
HPA052504

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
TERF1P542742EBI-355106,EBI-710997

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • heat shock protein binding Source: UniProtKB
  • unfolded protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109542, 88 interactors
IntActiP17066, 52 interactors
MINTiP17066
STRINGi9606.ENSP00000310219

Structurei

Secondary structure

1643
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi9 – 12Combined sources4
Beta strandi15 – 24Combined sources10
Beta strandi27 – 30Combined sources4
Beta strandi38 – 41Combined sources4
Beta strandi44 – 46Combined sources3
Beta strandi51 – 53Combined sources3
Helixi55 – 59Combined sources5
Turni60 – 63Combined sources4
Helixi65 – 67Combined sources3
Helixi72 – 74Combined sources3
Turni75 – 77Combined sources3
Helixi83 – 90Combined sources8
Beta strandi93 – 99Combined sources7
Beta strandi102 – 109Combined sources8
Beta strandi112 – 116Combined sources5
Helixi118 – 137Combined sources20
Beta strandi143 – 148Combined sources6
Helixi154 – 166Combined sources13
Beta strandi170 – 176Combined sources7
Helixi177 – 184Combined sources8
Turni185 – 188Combined sources4
Beta strandi195 – 202Combined sources8
Beta strandi207 – 215Combined sources9
Beta strandi218 – 227Combined sources10
Helixi232 – 251Combined sources20
Helixi259 – 275Combined sources17
Turni276 – 278Combined sources3
Beta strandi280 – 290Combined sources11
Beta strandi293 – 300Combined sources8
Helixi301 – 314Combined sources14
Helixi316 – 326Combined sources11
Helixi330 – 332Combined sources3
Beta strandi334 – 340Combined sources7
Helixi341 – 344Combined sources4
Helixi346 – 355Combined sources10
Turni356 – 358Combined sources3
Turni367 – 369Combined sources3
Helixi370 – 383Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3FE1X-ray2.20A/B/C6-385[»]
ProteinModelPortaliP17066
SMRiP17066
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17066

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni3 – 388Nucleotide-binding domain (NBD)By similarityAdd BLAST386
Regioni396 – 511Substrate-binding domain (SBD)By similarityAdd BLAST116

Domaini

The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.1 Publication

Sequence similaritiesi

Belongs to the heat shock protein 70 family.Curated

Phylogenomic databases

eggNOGiKOG0101 Eukaryota
COG0443 LUCA
GeneTreeiENSGT00910000144045
HOGENOMiHOG000228135
HOVERGENiHBG051845
InParanoidiP17066
KOiK03283
OMAiHFMEEFR
OrthoDBiEOG091G03SF
PhylomeDBiP17066
TreeFamiTF105042

Family and domain databases

Gene3Di1.20.1270.10, 1 hit
2.60.34.10, 1 hit
InterProiView protein in InterPro
IPR018181 Heat_shock_70_CS
IPR029048 HSP70_C_sf
IPR029047 HSP70_peptide-bd_sf
IPR013126 Hsp_70_fam
PANTHERiPTHR19375 PTHR19375, 1 hit
PfamiView protein in Pfam
PF00012 HSP70, 1 hit
PRINTSiPR00301 HEATSHOCK70
SUPFAMiSSF100920 SSF100920, 1 hit
SSF100934 SSF100934, 1 hit
PROSITEiView protein in PROSITE
PS00297 HSP70_1, 1 hit
PS00329 HSP70_2, 1 hit
PS01036 HSP70_3, 1 hit

Sequencei

Sequence statusi: Complete.

P17066-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQAPRELAVG IDLGTTYSCV GVFQQGRVEI LANDQGNRTT PSYVAFTDTE
60 70 80 90 100
RLVGDAAKSQ AALNPHNTVF DAKRLIGRKF ADTTVQSDMK HWPFRVVSEG
110 120 130 140 150
GKPKVRVCYR GEDKTFYPEE ISSMVLSKMK ETAEAYLGQP VKHAVITVPA
160 170 180 190 200
YFNDSQRQAT KDAGAIAGLN VLRIINEPTA AAIAYGLDRR GAGERNVLIF
210 220 230 240 250
DLGGGTFDVS VLSIDAGVFE VKATAGDTHL GGEDFDNRLV NHFMEEFRRK
260 270 280 290 300
HGKDLSGNKR ALRRLRTACE RAKRTLSSST QATLEIDSLF EGVDFYTSIT
310 320 330 340 350
RARFEELCSD LFRSTLEPVE KALRDAKLDK AQIHDVVLVG GSTRIPKVQK
360 370 380 390 400
LLQDFFNGKE LNKSINPDEA VAYGAAVQAA VLMGDKCEKV QDLLLLDVAP
410 420 430 440 450
LSLGLETAGG VMTTLIQRNA TIPTKQTQTF TTYSDNQPGV FIQVYEGERA
460 470 480 490 500
MTKDNNLLGR FELSGIPPAP RGVPQIEVTF DIDANGILSV TATDRSTGKA
510 520 530 540 550
NKITITNDKG RLSKEEVERM VHEAEQYKAE DEAQRDRVAA KNSLEAHVFH
560 570 580 590 600
VKGSLQEESL RDKIPEEDRR KMQDKCREVL AWLEHNQLAE KEEYEHQKRE
610 620 630 640
LEQICRPIFS RLYGGPGVPG GSSCGTQARQ GDPSTGPIIE EVD
Length:643
Mass (Da):71,028
Last modified:September 19, 2003 - v2
Checksum:iBCE348F0226DB70B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106 – 108RVC → PVS in CAA36061 (PubMed:2327978).Curated3
Sequence conflicti263R → G in CAA36061 (PubMed:2327978).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06071865P → T1 PublicationCorresponds to variant dbSNP:rs41297698Ensembl.1
Natural variantiVAR_06071995R → Q1 PublicationCorresponds to variant dbSNP:rs400835Ensembl.1
Natural variantiVAR_049605150A → T1 PublicationCorresponds to variant dbSNP:rs10919224Ensembl.1
Natural variantiVAR_049606153N → S1 PublicationCorresponds to variant dbSNP:rs10919225Ensembl.1
Natural variantiVAR_049607154D → N1 PublicationCorresponds to variant dbSNP:rs10919226Ensembl.1
Natural variantiVAR_060720159A → V1 PublicationCorresponds to variant dbSNP:rs41297702Ensembl.1
Natural variantiVAR_049608170N → K1 PublicationCorresponds to variant dbSNP:rs41297704Ensembl.1
Natural variantiVAR_049609173R → P1 PublicationCorresponds to variant dbSNP:rs41297708Ensembl.1
Natural variantiVAR_049610178P → A1 PublicationCorresponds to variant dbSNP:rs41297710Ensembl.1
Natural variantiVAR_049611194E → K1 PublicationCorresponds to variant dbSNP:rs41297714Ensembl.1
Natural variantiVAR_024182198L → F1 PublicationCorresponds to variant dbSNP:rs1079109Ensembl.1
Natural variantiVAR_049612260R → H. Corresponds to variant dbSNP:rs41299256Ensembl.1
Natural variantiVAR_060721297T → K1 PublicationCorresponds to variant dbSNP:rs41297718Ensembl.1
Natural variantiVAR_059360336V → F. Corresponds to variant dbSNP:rs417707Ensembl.1
Natural variantiVAR_049613464S → I1 PublicationCorresponds to variant dbSNP:rs388218Ensembl.1
Natural variantiVAR_049614471R → H1 PublicationCorresponds to variant dbSNP:rs41299256Ensembl.1
Natural variantiVAR_049615528K → E1 PublicationCorresponds to variant dbSNP:rs570189Ensembl.1
Natural variantiVAR_059361528K → R. Corresponds to variant dbSNP:rs570167Ensembl.1
Natural variantiVAR_024183562D → E1 PublicationCorresponds to variant dbSNP:rs753856Ensembl.1
Natural variantiVAR_049616572M → V. Corresponds to variant dbSNP:rs452004Ensembl.1
Natural variantiVAR_049617577R → Q1 PublicationCorresponds to variant dbSNP:rs368844Ensembl.1
Natural variantiVAR_049618626T → A1 PublicationCorresponds to variant dbSNP:rs41299260Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X51757 Genomic DNA Translation: CAA36061.1
X51758 mRNA Translation: CAA36062.1
DQ521571 Genomic DNA Translation: ABF47108.1
AL590385 Genomic DNA No translation available.
BC004279 mRNA Translation: AAH04279.1
BC035665 mRNA Translation: AAH35665.1
S78631 Genomic DNA No translation available.
CCDSiCCDS1231.1
PIRiS09036
RefSeqiNP_002146.2, NM_002155.4
UniGeneiHs.654614

Genome annotation databases

EnsembliENST00000309758; ENSP00000310219; ENSG00000173110
GeneIDi3310
KEGGihsa:3310
UCSCiuc001gaq.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHSP76_HUMAN
AccessioniPrimary (citable) accession number: P17066
Secondary accession number(s): Q1HBA8, Q8IYK7, Q9BT95
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: September 19, 2003
Last modified: April 25, 2018
This is version 169 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health